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LETTER TO EDITOR  
Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 268-269
Transient abnormal megakaryocytic hyperplasia secondary to all-trans retinoic acid therapy


1 Department of Oncopathology, Delhi State Cancer Institute, Delhi, India
2 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication3-Jul-2012
 

How to cite this article:
Jain M, Tyagi S. Transient abnormal megakaryocytic hyperplasia secondary to all-trans retinoic acid therapy. Indian J Pathol Microbiol 2012;55:268-9

How to cite this URL:
Jain M, Tyagi S. Transient abnormal megakaryocytic hyperplasia secondary to all-trans retinoic acid therapy. Indian J Pathol Microbiol [serial online] 2012 [cited 2020 Feb 25];55:268-9. Available from: http://www.ijpmonline.org/text.asp?2012/55/2/268/97911


Sir,

Chemotherapeutic drugs generally cause bone marrow suppression of variable degree. The common postchemotherapeutic morphological changes include megaloblastosis, dysmyelopoiesis, dyserythropoiesis, monocytosis, erythroid hyperplasia, and bone marrow fibrosis. [1] Megakaryocytic hyperplasia with dysmegakaryopoiesis is a rare event. Here, a case of acute promyelocytic leukemia (APML) in which uncommon morphological findings were noted during bone marrow recovery after treatment with all-trans retinoic acid (ATRA) are described.

A 20-year-old male presented with fever and bleeding gums for 15 days. On physical examination pallor, fever and bleeding gums were noted. Routine hemogram revealed Hb - 5.3g/dL, TLC - 25.7 × 10 3 /μL, and platelets - 38 × 10 3 /μL. Peripheral smear showed abnormal promyelocytes (70%) and blasts (9%) with presence of  Auer rods More Details. Bone marrow aspirate slide revealed more than 90% abnormal promyelocytes and blasts which were strongly positive for Sudan black, myeloperoxidase, and nonspecific esterase. He was diagnosed as a case of acute promyelocytic leukemia (APML). This was further confirmed by reverse transcriptase-PCR which was positive for pml-Rarα for t (15; 17). Combination chemotherapy was given using ATRA - 45 mg/m 2 /day orally starting from day 1 and daunorubicin - 60mg/m 2 /day intravenously for 3 days starting from day 4. At day 28 the patient was clinically in remission. The bone marrow done to assess the remission status showed features of differentiation and 8% blasts along with unusual features like megakaryocytic proliferation with dysmegakaryopoiesis in the form of hypolobated and hyperlobated forms with small separated nuclei and micromegakaryocytes [Figure 1]. Erythroid hyperplasia with reversal of myeloid:erythroid (M:E) ratio and dyserythropoeisis in form of binucleation and internuclear bridging was noted. Peripheral smear showed monocytosis. Bone marrow biopsy was also done; however, no fibrosis was noted. Therefore ATRA- 45mg/m2/day was continued and bone marrow was done on day 45, which was in remission and did not show the dyspoietic changes, noted earlier. There was normal granulocytic maturation and the megakaryocytic hyperplasia noted earlier at day 28 was absent.
Figure 1: Megakaryocytic hyperplasia with dysmegakaryopoeisis (Jenner Giemsa × 100)

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Megakaryocytic hyperplasia may be seen in various benign disorders like iron deficiency anemia, idiopathic thrombocytopenia, and autoimmune diseases, which are generally not associated with dysplasia. [2] Megakaryocytic hyperplasia along with dysplastic changes is a characteristic feature of malignant or clonal disorders and seen in several chronic myeloproliferative neoplasms like chronic myeloid leukemia, polycythemia vera, or essential thrombocytosis, myelodysplastic syndromes, early phase of myelofibrosis, and acute myelofibrosis. [3] It can be seen as a reactive phenomenon in patients of acute myeloid leukemia (AML) receiving chemotherapy. In the present case, megakaryocytic hyperplasia along with dysmegakaryopoiesis was not evident at diagnosis. On day 28, marrow after treatment with ATRA showed the above features and it disappeared on day 45.

The common features associated with ATRA therapy are hyperleukocytosis, monocytosis, and rarely bone marrow necrosis or collagenous fibrosis. Atypical megakaryocytic hyperplasia after ATRA treatment has not been described in the literature. Nancy et al. [4] in a study of 15 patients of AML described atypical megakaryocytic hyperplasia with dysmegakaryopoeisis in 13% cases following conventional (3 + 7) chemotherapy. Two of 15 cases were APML, but ATRA was not used as induction chemotherapy. None of the patients had AML-M7.

The finding of megakaryocytic hyperplasia in this case does not appear as part of early marrow regeneration because the degree of hyperplasia and dyspoeisis was greater than that is seen normally after chemotherapy. There was evidence of erythroid hyperplasia as well and myeloid maturation was minimally present leading to a reversal of M:E ratio. Generally erythroid cells are the prime target of chemotherapy; however, they are the first to regenerate as well. The megakaryocytes are known to regenerate last after chemotherapy.

Several possible explanations for post leukemic dyspoeisis exist. One possibility is the drug ATRA itself. Another possibility is that antileukemic drugs eradicate or suppress one malignant clone and alter bone marrow environment in such a way as to induce/facilitate development of another abnormal dyspoeitic clone. [5] Thus it is concluded that such a transient marrow finding may mimic chronic myeloproliferative neoplasm or MDS or megakaryoblastic leukemia in the absence of proper clinical history and may cause a diagnostic error. However, the significance of these findings are not known whether they are associated with relapse or poor prognosis and more studies are required to evaluate this.

 
   References Top

1.Foucar KM. Interpretation of post chemotherapy and post-transplantation bone marrowspecimens. In: Knowles DM, editor. Neoplastic Hematopathology. 2ed. Philadelphia, USA: Lippincott Williams and Wilkins; 2001. p. 1791-814.  Back to cited text no. 1
    
2.Krause JR. Megakaryocytes. In: Krause JR, editor. Bone marrow biopsy. New York: Churchill Livingstone; 1981. p. 76-83.  Back to cited text no. 2
    
3.Fialkow PJ, Jacobsen RJ, Papayannopoulou T. Chronic myelocytic leukemia: Clonal origin in a stem cell common to the granulocyte erythrocyte platelet and monocyte/ macrophage. Am J Med 1977;63:125-30.  Back to cited text no. 3
    
4.Rosenthal NS, Farhi DC. Dysmegakaryopoeisis resembling acute megakaryoblastic leukemia in treated acute myeloid leukemia. Am J Clin Pathol 1991;95:556-60.  Back to cited text no. 4
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5.Foucar K, Vaughan WP, Armitage JO, Patil S, Dick F, Karp JE. Post leukemic dysmyelopoesis. Am J Hematol 1983;15:321-34.  Back to cited text no. 5
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Correspondence Address:
Monica Jain
Department of Oncopathology, Delhi State Cancer Institute, Dilshaad Garden, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.97911

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